Levofloxacin is known to inhibit bacterial DNA gyrase and topoisomerase IV to inhibit the DNA synthesis, exhibiting an antibacterial activity. Levofloxacin exhibits a broad antibacterial spectrum and a potent antibacterial action, and has already been widely used in the form of 0.5% (w/v) levofloxacin ophthalmic solution (Cravit(registered trademark) ophthalmic solution 0.5%). This ophthalmic solution contains levofloxacin as an active ingredient, as well as sodium chloride and a pH adjuster as additives. The ophthalmic solution is adjusted to have a pH of 6.2 to 6.8 and an osmotic pressure ratio of 1.0 to 1.1. The solution has a clear appearance.
Meanwhile, dexamethasone is a synthetic corticosteroid having a potent anti-inflammatory action. Among water-soluble ester derivatives thereof, particularly dexamethasone sodium phosphate has been widely used in the form of 0.1% (w/v) dexamethasone sodium phosphate ophthalmic solution (Orgadrone(registered trademark) ophthalmic solution 0.1%). This ophthalmic solution contains dexamethasone sodium phosphate as an active ingredient, as well as benzalkonium chloride, sodium edetate hydrate, boric acid, borax, and an isotonic agent as additives. The ophthalmic solution is adjusted to have a pH of 7.4 to 8.4 and be iso-osmotic. The solution has a clear appearance.
Generally, in making a drug in the form of an ophthalmic aqueous composition such as an ophthalmic solution, there are many problems to be solved, including drug stability, drug migration, and so on.
Patent Literature 1 states that blending levofloxacin at a concentration of 1.0 to 3.0% (w/v) with glycerin at such a concentration (2 to 2.5% (v/v)) as to render the composition substantially iso-osmotic enhances the efficacy of antimicrobial preservation.
However, there have been no known ophthalmic aqueous composition which contains levofloxacin, a salt thereof, or a solvate thereof and dexamethasone, an ester thereof, or a salt thereof, and which solves the problems with drug stability, drug migration, and so on.